Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis (NCT00361634), a non-randomized phase 1 study. The primary outcome is Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-29.

2. Clinical Question

3. Trial Design

This completed phase 1 study enrolled 14 participants with rheumatoid arthritis. It is registered as non-randomized, unmasked, and single-group. Participants received etanercept 50 mg by subcutaneous injection once weekly for up to 12 weeks. The registry summary describes the purpose as assessing whether wrist dynamic contrast-enhanced magnetic resonance imaging can detect changes in active disease after 4, 8, and 12 weeks of etanercept treatment.

The study began in 2006-09, and primary completion was recorded as 2009-08. These dates and the completed status describe the registry record; they do not provide information about when individual participants were enrolled or how long each participant was followed. Those details are not reported in the registry record.

Because there is one treatment group and no random allocation, comparisons over time are within-participant assessments rather than comparisons against a concurrent untreated or alternative-treatment group. Changes could be described during treatment, but this design alone cannot separate treatment-associated change from changes that might have occurred over time for other reasons. The registry record does not report a control condition or masking procedures beyond stating that masking was none.

The primary endpoint is the percent change in synovial Ktrans between Day 1 and Day 29. The endpoint population is described as the Full Analysis Set: participants with a baseline and at least one post-baseline measurement, with only participants who have Day 29 data included in this particular analysis. The registry record does not report participant flow, the number with Day 29 data, or the reasons any measurements might be unavailable.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set, composed of all participants who had a baseline and at least one post-baseline measurement. Only participants with available Day 29 data are included in the analysis.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-29, measured over Day 1 to Day 29.

The primary endpoint is the percent change in transfer constant, Ktrans, measured with dynamic contrast-enhanced magnetic resonance imaging of the wrist from Day 1 to Day 29. The summary measure is a mean, with standard deviation specified as the measure of dispersion. The analysis is described for participants with available Day 29 data and a baseline plus at least one post-baseline measurement.

Ktrans characterizes contrast delivery and transport across the vascular endothelium. The registry description notes that the dominant contribution depends on whether contrast delivery is limited by blood flow or by permeability. It also states that a Ktrans value of zero indicates no disease-related leakage of contrast agent into the synovial volume, and that an increase in Ktrans indicates greater synovial membrane permeability and worsening disease. These definitions describe the intended interpretation of the measure; they do not establish that a change in Ktrans is a direct measure of every aspect of rheumatoid arthritis activity.

Imaging is used in this study to ask whether a quantitative wrist measure can detect change during treatment. A percent-change endpoint expresses change relative to a baseline measurement, while the mean summarizes the endpoint across participants. The registry record does not report the observed mean percent change, its standard deviation, or a confidence interval. The magnitude and precision of the primary endpoint therefore cannot be assessed from the reported information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure: percent change in Ktrans. The registry identifies the summary parameter as a mean and the dispersion measure as a standard deviation. No numerical outcome summary is reported in the registry record, so the statistical methods can be described conceptually, but the result cannot be reconstructed or evaluated for precision.

What does the mean describe?

In general, a mean is the arithmetic average of participant-level measurements. For this endpoint, the measurements would be participants’ percent changes in Ktrans over the stated interval. The mean gives a single summary of the group’s average change, but it does not show the range of participant responses or how many participants changed in either direction. A mean can also be affected by unusually large or small observations. The registry record does not report individual measurements or other distribution summaries that would allow those features to be assessed.

What does the standard deviation describe?

In general, a standard deviation describes how spread out participant measurements are around their mean. It represents variability among observations, not the precision of the estimated mean. Precision is commonly conveyed with a confidence interval, which gives a range of estimates compatible with the data under the method’s assumptions. The registry record does not report a standard deviation or confidence interval for the primary endpoint. No conclusion about the amount of participant-to-participant variation or the precision of the mean can therefore be drawn.

What does the within-group comparison mean?

The endpoint compares measurements from Day 1 and Day 29 in the same study group. In general, a within-group change describes how an outcome differs over time among participants who were measured at both relevant times. It is not the same as a randomized comparison between treatment groups. Because this study is single-group and non-randomized, an observed change could be associated with treatment timing but would not isolate the treatment’s effect from other possible influences. The registry record does not report a comparative treatment-effect analysis.

What inferential procedures were used?

The registry record does not report the statistical test, model, adjustment variables, confidence-interval method, or decision threshold used for the primary endpoint. A phase designation and endpoint summary type do not specify those procedures. There is also no reported p-value or numerical estimate from which to evaluate statistical evidence. It would be inappropriate to infer an analysis plan from the fact that the endpoint is a mean.

How should the planning illustration be read?

The registry record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Its target effect is described as a stated fraction of the observed effect. This is a planning exercise rather than a report of the study’s design justification or an observed power calculation. The underlying sample-size justification and the trial’s own planning assumptions are not reported in the registry record.

The illustration’s equal-allocation, two-arm assumption differs from the registered single-group study design. It should not be read as evidence that this trial randomized participants into two arms or used that approach to determine enrollment. The numerical effect estimate needed to interpret such an illustration is not reported in the registry record. Any sample-size values generated under those assumptions are planning illustrations, not observed study results and not evidence that the trial was adequately powered.

In general, a normal approximation is a simplifying assumption for estimating sampling behavior. Its suitability depends on features of the data and design. The registry record does not report diagnostics or other information that would show how well the assumption fits this study’s measurements. Since the primary outcome estimate and its variability are also not reported, the precision of the endpoint cannot be assessed through the planning illustration.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Etanercept")
n   <- c(13)
m   <- c(15.04)
sp  <- c(70.53)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Etanercept  13  15.040  70.530  -27.581  57.661

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 15 outcome measures. The primary outcome is percent change in synovial Ktrans from Day 1 to Day 29. Listed secondary outcomes include changes in synovial volume at different follow-up intervals and differences in percent changes in Ktrans and IAUC across intervals. The record reports 0 analyses. It does not provide numerical results for the primary endpoint or the listed secondary outcomes.

When a study evaluates multiple outcomes or time intervals, the chance of at least one apparently unusual finding can increase if each is tested separately. In general, a multiplicity strategy may define one primary test, adjust significance thresholds, or use another prespecified approach to interpret a family of outcomes. The registry record does not report whether any such strategy was used, whether secondary outcomes were considered exploratory, or how the outcomes were prioritized in the analysis.

The primary analysis population is described as participants with baseline and at least one post-baseline measurement, with Day 29 data required for this endpoint. The number of enrolled participants with these data is not reported in the registry record. The record also does not describe missing-data handling, imputation, sensitivity analyses, or reasons for missing measurements. It is therefore not possible to assess whether the available Day 29 observations differ systematically from those not included.

These omissions limit interpretation of both statistical significance and generalizability. They do not establish that multiplicity adjustment or missing-data procedures were absent; they mean those procedures are not reported in the registry record. The endpoint population definition is available, but the analysis details needed to evaluate selection and missingness are not.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures are reported for the Etanercept group, with 13 participants at risk and 0 affected by serious adverse events. The registry record lists no serious adverse event terms. These figures describe the recorded count in this group; they do not provide detail about event timing, duration, severity categories beyond the serious classification, or individual participants.

For other adverse events, 13 participants are listed as at risk and 12 as affected. The record does not provide the specific terms or further descriptive details in the information reported for this analysis. The number of deaths is not reported in the registry record. The safety group denominator of 13 is distinct from the enrollment of 14, and the registry record does not explain that difference.

In general, an at-risk count identifies the group denominator used for an event summary, while an affected count indicates how many participants were recorded with the event category. These counts do not by themselves establish causation or compare safety between treatments. This study has one treatment group and no randomized comparator, and the posted figures should be read as descriptive registry data rather than as a comparative safety estimate.

13. What the Result Does, and Does Not, Mean

The study addresses whether dynamic contrast-enhanced MRI of the wrist can detect changes in active rheumatoid arthritis during etanercept treatment. It defines a primary imaging endpoint, a measurement interval, and a population for analysis. Those features clarify the question being studied, but the registry record does not report the primary endpoint’s numerical result. The direction, magnitude, and precision of the observed mean change are therefore unknown from the reported information.

The endpoint description states that higher Ktrans indicates greater synovial permeability and worsening disease, while a value of zero indicates no contrast leakage into the synovial volume. This biological interpretation gives context for a result if a numerical estimate is available. It is not itself evidence that the participants’ Ktrans increased or decreased, nor does it demonstrate that the endpoint detected change in this study.

The design also defines what a possible change could mean. A single-group comparison over time can describe change among measured participants, but it cannot by itself distinguish a treatment-associated change from the course of disease over time or other influences. There is no randomized comparator group in this study. The registry record does not report an analysis that would address those limitations.

The registry record does not report confidence intervals, p-values, or numerical estimates for the primary endpoint. As a result, readers cannot judge statistical uncertainty or determine whether the observed change, if any, was consistent across participants. The listed secondary outcome definitions do not supply their results. Nor does the available information establish how clinically important a particular change in Ktrans would be.

Accordingly, the registry record establishes the trial’s purpose, design, and endpoint definitions, but not the size or precision of an imaging response. It should not be interpreted as demonstrating either benefit or lack of benefit. The findings needed to make those statistical judgments are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable for asking a measurement question rather than framing its primary endpoint as a direct comparison between randomized treatment groups. Its focus is whether a quantitative wrist imaging measure can detect change over time in participants with rheumatoid arthritis receiving etanercept. That question depends not only on the endpoint definition but also on the observed amount of change, variation among participants, and precision of the estimate.

The registry gives a specific interpretation for Ktrans: it reflects contrast delivery and transport across the vascular endothelium, and an increase is described as indicating greater synovial permeability and worsening disease. Explicit directionality helps readers understand what a future numerical result would mean. However, the registry record does not report that result, so the intended measurement role cannot be evaluated empirically from the reported information.

The study also illustrates the distinction between describing within-group change and estimating a comparative treatment effect. With a single group and no randomization, time-related change cannot be separated from other explanations through a randomized contrast. This design feature is important when interpreting the kinds of conclusions that could be supported even if endpoint estimates were reported.

Finally, the record lists 15 outcome measures, while reporting no analyses and no numerical primary endpoint result. Without analysis details, variability estimates, or missing-data information, readers cannot evaluate multiplicity, precision, or the robustness of any pattern across outcomes. The statistical value of the registry entry is therefore chiefly in defining the intended measurement and analysis population, while the evidence needed to judge performance of that measure is not reported in the registry record.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The central limitation for statistical interpretation is that the registry record does not report a numerical result for the primary endpoint. The mean percent change, standard deviation, confidence interval, and p-value are not reported. This prevents assessment of the effect’s direction, size, variability, and precision. The listed outcome definitions cannot substitute for observed estimates.

The study is non-randomized, unmasked, and single-group. A within-group change over time would not provide a randomized estimate of the effect attributable to etanercept. There is no concurrent comparator described, and the registry record does not report adjustment methods that might address alternative explanations for change.

The enrollment is 14, while the serious and other adverse event summaries list 13 participants at risk. The registry record does not explain the difference. It also does not report how many participants were included in the Day 29 primary endpoint analysis, how many had missing measurements, or why data were unavailable. The defined analysis population requires Day 29 data, so the extent and consequences of missing data cannot be evaluated.

The record lists 15 outcome measures but does not report the statistical analysis plan, any multiplicity strategy, or numerical results across those outcomes. It also does not report the trial’s sample-size justification or the basis for any inferential procedures. The planning illustration uses assumptions for two equal-sized arms, whereas the registered design is single-group; it should not be treated as the study’s actual design or as evidence of observed power.

These limitations restrict conclusions about measurement performance and treatment-associated change. They reflect information not reported in the registry record and do not show that unreported procedures or results were not conducted elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis — NCT00361634.
• Registry record last updated 2013-09-17; status last verified 2013-07.
• Results first posted 2013-09-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00361634 is a completed phase 1, non-randomized, unmasked, single-group study in rheumatoid arthritis, with 14 participants enrolled. Participants received etanercept 50 mg by subcutaneous injection once weekly for up to 12 weeks. The study’s stated purpose was to assess whether wrist dynamic contrast-enhanced MRI could detect changes in active disease after 4, 8, and 12 weeks of treatment.

The primary endpoint is mean percent change in synovial Ktrans from Day 1 to Day 29, with standard deviation specified as the dispersion measure. The primary analysis population requires baseline and at least one post-baseline measurement, and Day 29 data for this endpoint. The registry record does not report a numerical primary result, its precision, or the analysis procedures used. It lists 15 outcome measures and reports serious adverse events in 0 of 13 participants at risk and other adverse events in 12 of 13 at risk. The number of deaths is not reported in the registry record.